In vitro and in vivo evidence for a role of the P2X7 receptor in the release of IL-1β in the murine brain
Abstract The P2X7 receptor (P2X7 R) is a purinoceptor expressed predominantly by cells of immune origin, including microglial cells. P2X7 R has a role in the release of biologically active proinflammatory cytokines such as IL-1β, IL-6 and TNFα. Here we demonstrate that when incubated with lipopolysa...
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Published in | Brain, behavior, and immunity Vol. 22; no. 2; pp. 234 - 244 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Netherlands
Elsevier
01.02.2008
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Subjects | |
Online Access | Get full text |
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Summary: | Abstract The P2X7 receptor (P2X7 R) is a purinoceptor expressed predominantly by cells of immune origin, including microglial cells. P2X7 R has a role in the release of biologically active proinflammatory cytokines such as IL-1β, IL-6 and TNFα. Here we demonstrate that when incubated with lipopolysaccharide (LPS), glial cells cultured from brain of P2X7 R−/− mice produce less IL-1β compared to glial cells from brains of wild-type mice. This is not the case for TNFα and IL-6. Our results indicate a selective effect of the P2X7R gene deletion on release of IL-1β release but not of IL-6 and TNFα. In addition, we confirm that only microglial cells produce IL-1β, and this release is dependent on P2X7 R and ABC1 transporter. Because IL-1β is a key regulator of the brain cytokine network and P2X7 R is an absolute requirement for IL-1β release, we further investigated whether response of brain cytokines to LPS in vivo was altered in P2X7 R−/− mice compared to wild-type mice. IL-1β and TNFα mRNAs were less elevated in the brain of P2X7 R−/− than in the brain of wild-type mice in response to systemic LPS. These results show that P2X7R plays a key role in the brain cytokine response to immune stimuli, which certainly applies also to cytokine-dependent alterations in brain functions including sickness behavior. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 PMCID: PMC2908086 |
ISSN: | 0889-1591 1090-2139 |
DOI: | 10.1016/j.bbi.2007.08.007 |